1050. Mouse Embryonic Endothelial Progenitor Cells Home to Atherosclerotic Lesions after Intravenous Delivery

Abstract

The integrity of the endothelial monolayer plays a critical role in preventing the pathogenesis of atherosclerosis. This study was designed to investigate whether mouse embryonic endothelial progenitor cells (eEPCs) participate in endothelial repair and limit atherosclerotic lesion formation. We isolated mesodermal cells from C57BL/6 embryos at embryonic day 7.5, the onset of vasculogenesis. These isolated eEPCs displayed unlimited stem-cell-like growth and a stable phenotype in culture. RNA analysis showed that these cells express high levels of the stem cell markers cKit, Sca-1, and Flk-1, as well as the endothelial cell-specific genes Tie2, vWF, and ICAM-2. These cells also expressed high levels of the angiogenic factors VEGF- alpha and TGF-beta. eEPCs formed tube like structures when cultured in Matrigel with endothelial cell growth supplement. Furthermore, in vitro differentiation of eEPCs by retinoic acid and c-AMP activated a strong expression (>10-fold) of PSGL-1 (P- selectin glycoprotein ligand 1), which might play a significant role in homing of eEPCs in situ. We transduced eEPCs with AAV2/8-LacZ and injected 1 × 106 cells I.V. into genetically defined atherosclerosis susceptible mice (LDb; Ldlr-/-Apobec1-/-, n=3). eEPCs were detected in the aortic arch of the aorta where severe atherosclerotic lesions were present. This result indicates that eEPCs can home to the atherosclerotic lesion in vivo and may provide potential ways to interfere with lesion development.